Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4'-piperidine] based melanocortin subtype-4 receptor agonists

Liangqin Guo; Zhixiong Ye; Jian Liu; Shuwen He; Raman K Bakshi; Iyassu K Sebhat; Peter H Dobbelaar; Qingmei Hong; Tianying Jian; James P Dellureficio; Nancy N Tsou; Richard G Ball; David H Weinberg; Tanya MacNeil; Rui Tang; Constantin Tamvakopoulos; Qianping Peng; Howard Y Chen; Airu S Chen; William J Martin; D Euan MacIntyre; Alison M Strack; Tung M Fong; Matthew J Wyvratt; Ravi P Nargund

doi:10.1016/j.bmcl.2010.06.068

Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4'-piperidine] based melanocortin subtype-4 receptor agonists

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4895-900. doi: 10.1016/j.bmcl.2010.06.068. Epub 2010 Jun 17.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. [email protected]

PMID: 20621473
DOI: 10.1016/j.bmcl.2010.06.068

Abstract

Design, synthesis, and SAR of a series of 3H-spiro[isobenzofuran-1,4'-piperidine] based compounds as potent, selective and orally bioavailable melanocortin subtype-4 receptor (MC4R) agonists are disclosed.

MeSH terms

Administration, Oral
Animals
Brain / metabolism
Crystallography, X-Ray
Drug Evaluation, Preclinical
Humans
Molecular Conformation
Piperidines / chemical synthesis
Piperidines / chemistry*
Piperidines / pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Melanocortin, Type 4 / agonists*
Receptor, Melanocortin, Type 4 / metabolism
Spiro Compounds / chemistry
Structure-Activity Relationship

Substances

Piperidines
Receptor, Melanocortin, Type 4
Spiro Compounds
piperidine